Higher plasma levels of tenofovir and darunavir but not efavirenz in older patients
1 December 2011. Related: Conference reports, PK and drug interactions, EACS 13 Belgrade 2011.
Simon Collins, HIV i-Base
Several studies looked at the association between older age and antiretroviral pharmacokinetics (PK).
Tenofovir
Muge Cevik from the Chelsea and Westminster Hospital London reported results from a PK study suggesting that tenofovir clearance is significantly reduced with increasing age and resulting in higher drug levels (AUC and Ctrough). [1]
This included steady-state plasma levels from 52 men and 2 women (12 of whom were on PI/r-based combinations). Median age was 54 years (range 40?81 years) with only two people younger than 50. Samples were drawn randomly and population pharmacokinetics applied to predict values.
Tenofovir median clearance (CL/F), AUC (24hr) and Ctrough (C24) were 110.0 L/r (27.4?248.3). 2.2 mg.hr/L (1.0?9.0), and 0.06 mg/L (0.01?0.3) respectively.
Increasing age was significantly associated with slower clearance (p=0.0012), higher AUC (p=0.0012) and higher Ctrough (p=0.0017). People older than 60 had significantly lower clearances (p=0.0447) and higher AUC (p=0.0457) than those younger than 60.
No PK differences were seen between PI and NNRTI based combinations (p=0.08).
Efavirenz and darunavir/ritonavir
A similar analysis was presented by Ahmed and colleagues from the same group at Chelsea and Westminster on the PK of efavirenz or darunavir/ritonavir used by older patients (median age was 54 years (range 27-77) and 56 years (28-76), respectively). [2]
In 70 men and 7 women taking efavirenz, no differences were seen in any PK parameter when comparisons were made between people older and younger than 50 (all p-values >0.05 for between age comparisons).
In 33 men and one woman taking darunavir/ritonavir (23 using once-daily) oral clearance was significantly lower in people over 50 years old (10.3 vs 13.0 L/h; p=0.027) with higher AUC (80.9 vs 61.6 mg.h/L; p=0.021) and Ctrough levels (1.9 vs 1.2 mg/L; p=0.008) than those younger than 50.
Once-daily vs twice-daily could not be assessed because of unequal age distribution between the two dosing regimens.
References:
- Cevik M et al. Tenofovir (TFV) pharmacokinetics (PK) in HIV infected individuals over 40 years of age. 13th EACS, 12?15 October 2011, Belgrade. Abstract PS 6/1.
- Ahmed A et al. Efavirenz and Darunavir Plasma Concentrations in HIV-infected Patients Aged 50 Years or over. 13th EACS, 12?15 October 2011, Belgrade. Abstract PE6.2/1.